Interferon-gamma (INF-gamma) gene expression was directed to the lens of transgenic mice with the murine alphaA-crystallin promoter. The transgenic mice obtained exhibited severe microphthalmia and microphakia; the lens architecture was disorganized, and lens-fiber cells were replaced by balloon cells. Differentiation of the neuroretina into inner and outer neuroblastic layers was arrested at the embryonic stage. Retinal detachment and the presence of macrophages in the subretinal space was observed in the adult mouse eye. The ectopic expression of IFN-gamma in the transgenic mouse eye induced major histocompatibility complex (MHC) class II gene expression in the eye and arrested differentiation of lens and retina cell lineages. Our data suggest that IFN-gamma can also regulate gene expression in nonlymphoid tissues and provide an animal model for studying the roles of IFN-gamma and MHC class II in ocular autoimmune diseases.